赛妥珠单抗聚乙二醇治疗克罗恩病患者：来自SECURE注册研究的最终安全性数据。
Certolizumab Pegol Treatment in Patients With Crohn's Disease: Final Safety Data From the SECURE Registry.
作者信息
Lichtenstein Gary R, Lee Scott D, Feagan Brian G, Loftus Edward V, Ng Samson, Dehlin Kaitlin, Quinn Paul, Coarse Jason, Rosario-Jansen Theresa, Arendt Catherine, Stark Jeffrey L
机构信息
Division of Gastroenterology and Hepatology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Division of Gastroenterology, University of Washington School of Medicine, Seattle, WA, USA.
出版信息
Crohns Colitis 360. 2025 Jan 25;7(1):otae083. doi: 10.1093/crocol/otae083. eCollection 2025 Jan.
BACKGROUND
Crohn's disease (CD) treatment is associated with increased risks of infection and malignancies. Although the safety of certolizumab pegol (CZP) is well established, long-term data from community-based observational studies are lacking.
AIM
This study aimed to evaluate long-term safety outcomes of patients from the SECURE registry receiving CZP relative to other CD treatments, including corticosteroids, immunosuppressants, and biologics. The primary outcome of this observational study was the evaluation of malignancies.
METHODS
Adult patients with CD were prospectively monitored for up to 8 years. Pre-specified data were collected for all enrolled patients. Adverse events of interest (AEoIs) were reported per 100 patient-years (PY) of exposure. Incidence rate ratios (IRRs) were calculated for AEoIs using multivariate regression analysis accounting for exposure to multiple treatments. Malignancies reported after any exposure to CZP were attributed to CZP. Post-hoc analyses were conducted to evaluate non-melanoma skin cancer (NMSC), lymphoma, and pregnancy outcomes.
RESULTS
A total of 3072 patients were enrolled in the study. The risk of AEoIs was similar between patients with only CZP exposure versus comparator exposure. Among patients with any CZP exposure, there was a higher frequency of serious infections (IRR: 2.56 [95% confidence interval (CI): 2.00, 3.29]) and hypersensitivity or anaphylactic reactions (IRR: 4.11 [95% CI: 1.80, 9.38]) versus patients with comparator exposure. Malignancy rates were similar across groups; however, concomitant use of thiopurines was associated with higher odds of NMSC (odds ratio: 2.30 [95% CI: 1.09, 4.89]). Most cases of lymphoma (5/7) occurred in patients with exposure to thiopurines. Pregnancy outcomes were similar across groups.
CONCLUSIONS
No new safety signals were identified for CZP; the use of thiopurines was identified as a risk factor for NMSC.
TRIAL REGISTRATION
NCT00844285.
背景
克罗恩病（CD）的治疗与感染和恶性肿瘤风险增加相关。尽管赛妥珠单抗（CZP）的安全性已得到充分证实，但缺乏基于社区的观察性研究的长期数据。
目的
本研究旨在评估来自SECURE注册研究的接受CZP治疗的患者相对于其他CD治疗（包括皮质类固醇、免疫抑制剂和生物制剂）的长期安全性结局。这项观察性研究的主要结局是对恶性肿瘤的评估。
方法
对成年CD患者进行了长达8年的前瞻性监测。收集了所有入组患者的预先指定的数据。按每100患者年（PY）暴露时间报告感兴趣的不良事件（AEoI）。使用多变量回归分析计算AEoI的发病率比（IRR），该分析考虑了多种治疗的暴露情况。任何接触CZP后报告的恶性肿瘤均归因于CZP。进行了事后分析以评估非黑色素瘤皮肤癌（NMSC）、淋巴瘤和妊娠结局。
结果
共有3072例患者入组本研究。仅暴露于CZP的患者与暴露于对照药物的患者相比，AEoI风险相似。在任何接触过CZP的患者中，与暴露于对照药物的患者相比，严重感染（IRR：2.56 [95%置信区间（CI）：2.00，3.29]）以及超敏反应或过敏反应（IRR：4.11 [95% CI：1.80，9.38]）的发生频率更高。各组的恶性肿瘤发生率相似；然而，硫嘌呤类药物的联合使用与NMSC的较高几率相关（优势比：2.30 [95% CI：1.09，4.89]）。大多数淋巴瘤病例（5/7）发生在接触硫嘌呤类药物的患者中。各组的妊娠结局相似。
结论
未发现与CZP相关的新的安全信号；硫嘌呤类药物的使用被确定为NMSC的一个风险因素。
试验注册
NCT00844285。
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